Year: 2012
Type: article
Study design: Observational Study
Abstract: INTRODUCTION: A younger age at menarche and an older age at menopause are well established risk factors for breast cancer. Recent genome-wide association studies have identified several novel genetic loci associated with these two traits. However, the association between these loci and breast cancer risk is unknown. METHODS: In this study, we investigated 19 and 17 newly identified single nucleotide polymorphisms (SNPs) from the ReproGen Consortium that have been associated with age at menarche and age at natural menopause, respectively, and assessed their associations with breast cancer risk in 6 population-based studies among up to 3,683 breast cancer cases and 34,174 controls in white women of European ancestry. In addition, we used these SNPs to calculate genetic risk scores (GRSs) based on their associations with each trait. RESULTS: After adjusting for age and potential population stratification, two age at menarche associated SNPs (rs1079866 and rs7821178) and one age at natural menopause associated SNP (rs2517388) were associated with breast cancer risk (p values, 0.003, 0.009 and 0.023, respectively). The odds ratios for breast cancer corresponding to per-risk-allele were 1.14 (95% CI, 1.05 to 1.24), 1.08 (95% CI, 1.02 to 1.15) and 1.10 (95% CI, 1.01 to 1.20), respectively, and were in the direction predicted by their associations with age at menarche or age at natural menopause. These associations did not appear to be attenuated by further controlling for self-reported age at menarche, age at natural menopause, or known breast cancer susceptibility loci. Although we did not observe a statistically significant association between any GRS for reproductive aging and breast cancer risk, the 4th and 5th highest quintiles of the younger age at menarche GRS had odds ratios of 1.14 (95% CI, 1.01 to 1.28) and 1.13 (95% CI, 1.00 to 1.27), respectively, compared to the lowest quintile. CONCLUSIONS: Our study suggests that three genetic variants, independent of their associations with age at menarche or age at natural menopause, were associated with breast cancer risk and may contribute modestly to breast cancer risk prediction; however, the combination of the 19 age at menarche or the 17 age at natural menopause associated SNPs did not appear to be useful for identifying a high risk subgroup for breast cancer.
Source: Breast Cancer Research
DOI: 10.1186/bcr3155
Authors: Chunyan He, Daniel I Chasman, Jill Dreyfus, Shih-Jen Hwang, Rikje Ruiter, Serena Sanna, Julie E Buring, Lindsay Fernández-Rhodes, Nora Franceschini, Susan E Hankinson, Albert Hofman, Kathryn L Lunetta, Giuseppe Palmieri, Eleonora Porcu, Fernando Rivadeneira, Lynda M Rose, Greta L Splansky, Lisette Stolk, André G Uitterlinden, Stephen J Chanock, Laura Crisponi, Ellen W Demerath, Joanne M Murabito, Paul M Ridker, Bruno H Stricker, David J Hunter
Institutions: Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis, Brigham and Women's Hospital, Harvard University, University of Minnesota, National Heart, Lung, and Blood Institute, Framingham Heart Study, Erasmus MC, Institute of Genetic and Biomedical Research, National Research Council, University of North Carolina at Chapel Hill, Boston University, Istituto di Chimica Biomolecolare, Netherlands Consortium for Healthy Ageing, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Broad Institute, Massachusetts Institute of Technology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,190
Funders: Amgen, School of Medicine, Boston University, European Commission, Fondation Leducq, ZonMw, Erasmus Medisch Centrum, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Cancer Institute, National Center for Research Resources
Awards: G1083489883, G118440752, G136105103, G1449130676, G1495020029, G1528515809, G1663676665, Atherosclerosis Risk in Communities Study (ARIC), G215333750, G2219366524, Institute for Clinical and Translational Research (UL1), G250621538, CCSP FIELD CENTER, G25881238, COMMUNITY AND COHORT SURVEILLANCE PROGRAM, CENTRAL HEMOSTATIS LABORATORY FOR CCSP, G2918387404, G300339986, G3205625555, G3540777072, G36937976, GWA for Gene-Environment Interaction Effects Influencing CHD, G37846424, G3839646794, G395156118, G4174427447, Atherosclerosis Risk in Communities Study (ARIC), G4824283243, G494123624, G528395701, G5369020747, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5457026379, G552178769, Epidemiology of Venous Thrombosis and Pulmonary Embolism, G558986044, G5636245874, Atherosclerosis Risk in Communities Study (ARIC), Genetics of Reproductive Life Period and Health Outcomes, The Framingham Heart Study, TRIAL OF ASPIRIN AND VITAMIN E IN WOMEN, G6902273418, G7364523043, Characterizing Genetic Susceptibility to Breast and Prostate Cancer; the BPC3, G7693351332, G77250574, G786153652, Women's Health Study: Continued Follow-up, G793702358, G7962241407, G80149192, G824087253, G8276458029, G8506930532, Building on GWAS for NHLBI-disease: the CHARGE consortium, G890705022, G8927421343, G9000015747, G9000028264, G9000080822, G9000108254, G9000124674, G9000126117, G9000152345, G9000294209, G9000332794, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G947029668, Atherosclerosis Risk in Communities Study (ARIC)
OpenAlex ID: W2102578254